RESUMO
Data from the general population suggest that fatality rates declined during the course of the pandemic. This analysis, using data extracted from the Brazilian Kidney Transplant COVID-19 Registry, seeks to determine fatality rates over time since the index case on March 3rd, 2020. Data from hospitalized patients with RT-PCR positive SARS-CoV-2 infection from March to August 2020 (35 sites, 878 patients) were compared using trend tests according to quartiles (Q1: <72 days; Q2: 72-104 days; Q3: 105-140 days; Q4: >140 days after the index case). The 28-day fatality decreased from 29.5% (Q1) to 18.8% (Q4) (pfor-trend = 0.004). In multivariable analysis, patients diagnosed in Q4 showed a 35% reduced risk of death. The trend of reducing fatality was associated with a lower number of comorbidities (20.7-10.6%, p for-trend = 0.002), younger age (55-53 years, pfor-trend = 0.062), and better baseline renal function (43.6-47.7 ml/min/1.73 m2, pfor-trend = 0.060), and were confirmed by multivariable analysis. The proportion of patients presenting dyspnea (pfor-trend = 0.001) and hypoxemia (pfor-trend < 0.001) at diagnosis, and requiring intensive care was also found reduced (pfor-trend = 0.038). Despite possible confounding variables and time-dependent sampling differences, we conclude that COVID-19-associated fatality decreased over time. Differences in demographics, clinical presentation, and treatment options might be involved.
Assuntos
COVID-19 , Transplante de Rim , Estudos de Coortes , Humanos , Transplante de Rim/efeitos adversos , Sistema de Registros , SARS-CoV-2 , TransplantadosRESUMO
BACKGROUND: Children and adolescents undergoing kidney transplantation may present oral conditions after the procedure, but a few studies have recently described them. AIM: To describe the oral conditions of post-renal transplant children and adolescents. DESIGN: Two calibrated dentists examined all the participants by assessing caries experience, enamel defects, periodontal condition and soft tissue lesions. RESULTS: A total of 120 participants were included in the study, in which 63 (52.5%) were male and 57 (47.5%) were female, with a mean age of 12.78 ± 3.9 years. Among the participants, 104 (86.7%) showed at least one oral change directly related to kidney disease. The most frequent oral findings were enamel defect (49/120; 40.8%) and drug-induced gingival overgrowth (DIGO) (20/120; 16.7%). Gingival bleeding was observed on probing in 115 (95.8%) participants, whereas 69 (57.5%) presented dental calculus and 51 (42.5%) had caries experience. CONCLUSION: Gingival bleeding, enamel defects and DIGO were the most frequent oral findings in kidney transplant children and adolescents. The use of amlodipine and anticonvulsants was associated with DIGO, and there was a positive correlation between oral ulcers and use of everolimus.
Assuntos
Cárie Dentária , Crescimento Excessivo da Gengiva , Transplante de Rim , Doenças Dentárias , Adolescente , Anlodipino/efeitos adversos , Anticonvulsivantes/efeitos adversos , Criança , Everolimo/efeitos adversos , Feminino , Crescimento Excessivo da Gengiva/induzido quimicamente , Crescimento Excessivo da Gengiva/patologia , Humanos , Transplante de Rim/efeitos adversos , Masculino , Saúde BucalRESUMO
This retrospective multicenter (n = 18) cohort study evaluated the incidence, risk factors, and the impact of delayed graft function (DGF) on 1-year kidney transplant (KT) outcomes. Of 3992 deceased donor KT performed in 2014-2015, the incidence of DGF was 54%, ranging from 29.9% to 87.7% among centers. Risk factors (lower-bound-95%CI OR upper-bound-95%CI ) were male gender (1.066 1.2491.463 ), diabetic kidney disease (1.053 1.2961.595 ), time on dialysis (1.005 1.0071.009 ), retransplantation (1.035 1.3971.885 ), preformed anti-HLA antibodies (1.011 1.3831.892 ), HLA mismatches (1.006 1.0661.130 ), donor age (1.011 1.0171.023 ), donor final serum creatinine (sCr) (1.239 1.3171.399 ), cold ischemia time (CIT) (1.031 1.0431.056 ), machine perfusion (0.401 0.5420.733 ), and induction therapy with rabbit antithymocyte globulin (rATG) (0.658 0.8000.973 ). Duration of DGF > 4 days was associated with inferior renal function and DGF > 14 days with the higher incidences of acute rejection, graft loss, and death. In conclusion, the incidence and duration of DGF were high and associated with inferior graft outcomes. While late referral and poor donor maintenance account for the high overall incidence of DGF, variability in donor and recipient selection, organ preservation method, and type of induction agent may account for the wide variation observed among transplant centers.
Assuntos
Transplante de Rim , Brasil/epidemiologia , Estudos de Coortes , Função Retardada do Enxerto/epidemiologia , Função Retardada do Enxerto/etiologia , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Incidência , Transplante de Rim/efeitos adversos , Masculino , Estudos Retrospectivos , Fatores de Risco , Doadores de TecidosRESUMO
OBJECTIVES: To describe the incidence of cytomegalovirus (CMV) infection/disease in kidney transplant recipients receiving an mTOR-inhibitor-containing immunosuppressive regimen without prophylactic CMV treatment. METHODS: This single-center retrospective cohort analysis included all de novo kidney transplant recipients (09/15/2015-07/31/2017) receiving 3 mg/kg single dose of rabbit antithymocyte globulin induction, tacrolimus, everolimus, and prednisone. Preemptive therapy was initiated only in patients deemed at higher risk for CMV infection: (a) D+/R- CMV patients; (b) after treatment for acute rejection (ARt); and (c) after everolimus discontinuation (EVRd). RESULTS: Of 230 patients, there were no episodes of CMV disease among 217 (94%) without criteria to initiate preemptive therapy. Of 77 (33.5%) patients initiating preemptive therapy, 13 were D+/R-, 30 were ARt, and 34 were EVRd. The overall incidence of first CMV infection/disease was 6% (46.1% in D+/R-, 13.3% ARt [all patients had also discontinued everolimus], and 11.8% after early [<90 days] EVRd). The incidence of biopsy-proven acute rejection was 5.6%, and median glomerular filtration rate at month 12 was 47 mL/min/1.73m2 . One-year patient and death-censored graft survivals were 97.4% and 98.1%. CONCLUSION: This study suggests that everolimus-containing immunosuppressive regimen reduces the need for preventive strategies for CMV infection in the majority of kidney transplant recipients, reducing antiviral drug-associated toxicities and healthcare-related expenditures.
Assuntos
Infecções por Citomegalovirus/tratamento farmacológico , Citomegalovirus/isolamento & purificação , Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/administração & dosagem , Transplante de Rim/efeitos adversos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Adulto , Soro Antilinfocitário/administração & dosagem , Brasil/epidemiologia , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/microbiologia , Everolimo/administração & dosagem , Feminino , Seguimentos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prednisona/administração & dosagem , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Tacrolimo/administração & dosagemRESUMO
Early hospital readmission (EHR) is associated with increased mortality after kidney transplantation. This is influenced by population demographics and the comprehensiveness of the healthcare system. We investigated the incidence and risk factors associated with EHR and 1-year patient and graft survivals. METHODS: We included all recipients of kidney transplant between 2011 and 2012. We excluded recipients younger than 18 years, retransplants and who died or lost the graft during the index hospital admission. RESULTS: Among 1175 recipients, the incidence of EHR was 26.6%. The main reasons for EHR were infection (67%), surgical complications (14%), and metabolic disturbances (11%). Independent risk factors associated with EHR were recipient age (OR = 1.95, 95% CI 1.46-2.63, P < 0.001), CMV serology negative (OR = 2.2, 95% CI 1.31-3.65, P = 0.003), use of rabbit anti-thymocyte globulin (OR = 2.06, 95% CI 1.33-3.13, P < 0.001), treatment for acute rejection during index hospitalization (OR = 1.68, 95% CI 1.15-2.47, P = 0.008), and length of stay (OR = 1.72, 95% CI 1.18-2.5, P = 0.005). Patient (88.8% vs 97.6%, P < 0.001) and death-censored graft (97.4% vs 99.0%, P < 0.001) survivals were inferior comparing patients with and without EHR. Conclusion EHR was independently associated with mortality (OR 4.01, 95% CI 2.13-7.54, P < 0.001), but its incidence and causes are directly related to the local characteristics of the population and healthcare system.
Assuntos
Rejeição de Enxerto/diagnóstico , Hospitalização/estatística & dados numéricos , Falência Renal Crônica/cirurgia , Transplante de Rim/mortalidade , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias , Prática de Saúde Pública/estatística & dados numéricos , Adulto , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
BACKGROUND: Urinary tract infections are frequent complications early after kidney transplantation, and the use of antimicrobial coated catheters in settings other than transplantation has shown promising results for infection prevention. The purpose of this study was to compare the efficacy of Nitrofurazone-coated silicone urinary catheters with non-impregnated silicone urinary catheters in reducing bacteriuria and urinary tract infections in kidney transplant recipients. METHODS: This single-center study, randomized controlled trial at the Hospital do Rim, a tertiary referral center in kidney transplantation, located in São Paulo, Brazil. Subjects involved living donor kidney transplant recipients, and were randomized 1:1 ratio with a computer-generated system to a Nitrofurazone-coated silicone urinary catheter and non-impregnated silicone urinary catheter from March 2013 to December 2014. Patients with asymptomatic bacteriuria or urinary tract infection at baseline, deceased kidney transplant donors, patients with known hypersensitivity to nitrofurantoin, pregnancy, and those refusing to sign the informed consent form were excluded from the study. RESULTS: Two hundred fourteen subjects were randomized and one hundred seventy-six completed the study. There were no differences in the rates of asymptomatic bacteriuria (12.5% in the Nitrofurazone group and 11.4% in the control group, P = 0.99) and urinary tract infection (8% and 6.8%, P = 0.99) and the incidence of side effects was more frequent in the Nitrofurazone-impregnated silicone urinary catheter group (46.6% and 26.1%, P = 0.007). CONCLUSION: The study suggests that there is no beneficial effect of the employment of Nitrofurazone-coated urinary catheter. TRIAL REGISTRATION NUMBER: ISRCTN57888785.
Assuntos
Antibacterianos/administração & dosagem , Transplante de Rim , Nitrofurazona/administração & dosagem , Cateteres Urinários , Adolescente , Adulto , Bacteriúria/prevenção & controle , Infecções Relacionadas a Cateter/prevenção & controle , Cateteres de Demora/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Silicones , Transplantados , Infecções Urinárias/prevenção & controle , Adulto JovemRESUMO
BACKGROUND: Late cytomegalovirus infections (LCMV) after the cessation of prophylaxis are well described. We aimed to assess clinical and epidemiological data on late-occurring cytomegalovirus (CMV) infections in the absence of CMV prophylaxis in a cohort of kidney transplant patients. METHODS: In a cohort of kidney transplant recipients not employing CMV-specific prophylaxis, patients with CMV infections occurring after 6 months of transplantation were compared to patients with CMV infections diagnosed within the first 6 months (early infections). The main objectives were to compare clinical outcomes and evaluate risk factors for late CMV infection. RESULTS: A total of 556 patients were evaluated. Forty-three patients with LCMV infections were compared to 513 patients with early CMV infections. LCMV infections occurred after a median of 473 days of transplantation and had a more severe course, with a statistically significant higher rate of invasive disease and graft loss (60.5% vs 21.6% and 11.6% vs 3.1% respectively). Thirty-day mortality was twice as high for patients with LCMV, but did not reach statistical significance (9.3% vs 4.3%). By multivariate analysis, employment of antilymphocyte therapy early after transplantation and tacrolimus as initial immunosuppressive therapy were significantly protective for the occurrence of LCMV infections. CONCLUSION: Late CMV infections in the absence of specific prophylaxis after kidney transplantation have a more severe outcome when compared to early infections and occur in patients less immunosuppressed early after transplantation.
Assuntos
Infecções por Citomegalovirus/epidemiologia , Transplante de Rim/efeitos adversos , Adulto , Citomegalovirus/efeitos dos fármacos , Infecções por Citomegalovirus/mortalidade , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , TransplantadosRESUMO
As the number of kidney transplants continues to rise, so does the number and complexities of surgical-related complications, which may be associated with increased morbidity and potentially graft loss. Ureteral stenosis, the most prevalent urological complication, may require diverse techniques for surgical correction depending on several recipient and graft abnormalities. Here we report the surgical and clinical outcomes of a 62-year-old man with a posttransplant pyeloureterostomy stricture successfully treated with ureterocalicostomy after a lower pole nephrectomy. Although the resection of renal parenchyma may prevent a stenosis recurrence, surgeons can be reluctant to use this strategy due to the possible negative impact on renal function. We highlight some key steps of the surgical technique to prevent unnecessary allograft lesion and present short-term outcomes, suggesting that this rarely described procedure is a safe and effective alternative treatment for kidney transplant recipients with pyeloureterostomy stenosis.
Assuntos
Transplante de Rim/efeitos adversos , Nefrectomia/métodos , Complicações Pós-Operatórias/prevenção & controle , Doenças Ureterais/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Prognóstico , Doenças Ureterais/etiologia , Doenças Ureterais/patologiaRESUMO
BACKGROUND: The use of mTOR inhibitors is associated with lower incidence of CMV infections but its effect on viral load has not been investigated. AIMS, MATERIALS AND METHODS: This post-hoc analysis included data from 273 CMV seropositive kidney transplant recipients randomized to receive anti-thymocyte globulin and everolimus (rAGT/TAC/EVR, n = 81), basiliximab and everolimus (BAS/TAC/EVR, n = 97) or basiliximab and mycophenolate (BAS/TAC/MPS, n = 95). All patients received tacrolimus (TAC) and corticosteroids. Preemptive CMV therapy based on weekly pp65 antigenemia test was used during the first 6 months. Blinded weekly CMV DNAemia was compared among the groups. RESULTS: The proportion of patients with undetectable CMV DNAemia (23.4% vs 56.7% vs 22.1%, P < .001) was higher in the BAS/TAC/EVR. The median number of study visits with positive CMV DNAemia (2.0 vs 0.0 vs 4.6, rATG/EVR vs BAS/MPS, P = .354; BAS/EVR vs BAS/MPS, P < .0001; rATG/EVR vs BAS/EVR, P < .001) were lower in the BAS/TAC/EVR. The proportion of patients with positive CMV DNAemia who were not treat for CMV infection/disease based on pp65 antigenemia was higher in rATG/TAC/EVR group (74.1% vs 36.1% vs 44.2%, P < .001) but mean CMV DNAemia was comparable to BAS/TAC/EVR and lower than BAS/TAC/MPS (8536 ± 15 899 vs 7975 ± 17 935 vs 16 965 ± 37 694 copies/mL, P < .05), respectively. The proportion of patients with CMV DNAemia below 5000 copies/mL was higher in patients receiving EVR (74.1% vs 83.5% vs 50.0%, P = .000), respectively. DISCUSSION AND CONCLUSION: These data suggest that mTOR inhibitors reduce the incidence of CMV infection by limiting CMV viral replication.
Assuntos
Soro Antilinfocitário/farmacologia , Infecções por Citomegalovirus/tratamento farmacológico , Everolimo/farmacologia , Imunossupressores/farmacologia , Carga Viral/efeitos dos fármacos , Adulto , Soro Antilinfocitário/uso terapêutico , Citomegalovirus/efeitos dos fármacos , Citomegalovirus/isolamento & purificação , Citomegalovirus/fisiologia , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/virologia , Everolimo/uso terapêutico , Feminino , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Incidência , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Testes Sorológicos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Resultado do Tratamento , Replicação Viral/efeitos dos fármacosRESUMO
Pneumocystis jirovecii can cause severe potentially life-threatening pneumonia (PCP) in kidney transplant patients. Prophylaxis of patients against PCP in this setting is usually performed during 6 months after transplantation. The aim of this study is to describe the molecular epidemiology of a cluster of PCP in renal transplant recipients in Brazil. Renal transplant patients who developed PCP between May and December 2011 had their formalin-fixed paraffin-embedded (FFPE) lung biopsy samples analysed. Pneumocystis jirovecii 23S mitochondrial large subunit of ribosomal RNA (23S mtLSU-rRNA), 26S rRNA, and dihydropteroate synthase (DHPS) genes were amplified by polymerase chain reaction (PCR), sequenced, and analysed for genetic variation. During the study period, 17 patients developed PCP (only four infections were documented within the first year after transplantation) and six (35.3%) died. Thirty FFPE samples from 11 patients, including one external control HIV-infected patient, had fungal DNA successfully extracted for further amplification and sequencing for all three genes. A total of five genotypes were identified among the 10 infected patients. Of note, four patients were infected by more than one genotype and seven patients were infected by the same genotype. DNA extracted from FFPE samples can be used for genotyping; this approach allowed us to demonstrate that multiple P. jirovecii strains were responsible for this cluster, and one genotype was found infecting seven patients. The knowledge of the causative agents of PCP may help to develop new initiatives for control and prevention of PCP among patients undergoing renal transplant and improve routine PCP prophylaxis.
Assuntos
Variação Genética , Transplante de Rim/efeitos adversos , Pneumocystis/isolamento & purificação , Pneumonia por Pneumocystis/microbiologia , Complicações Pós-Operatórias/microbiologia , Adulto , Brasil , Estudos Transversais , DNA Fúngico/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Pneumocystis/classificação , Pneumocystis/genética , Pneumonia por Pneumocystis/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Estudos Retrospectivos , Subunidades Ribossômicas Maiores/genética , Adulto JovemRESUMO
INTRODUCTION: There is a paucity of data regarding the complications in kidney transplant patients who may require intensive care unit (ICU) management, despite being the most common solid organ transplant worldwide. OBJECTIVE: To identify the main reasons for ICU admission and to determine the factors associated with hospital mortality in kidney transplant recipients. DESIGN: This single-center retrospective cohort study was conducted between September 2013 and June 2014, including all consecutive kidney transplant patients requiring ICU admission. We collected data on patient demographics, transplant characteristics, clinical data, and prognostic scores. The independent determinants of hospital mortality were identified by multiple logistic regression analysis. We also assessed the performance of Simplified Acute Physiology Score 3 (SAPS 3) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. RESULTS: We analyzed data from 413 patients, the majority of whom were admitted late after renal transplantation (1169 days; 63-3003 days). The main reason for admission was sepsis (33.2%), followed by cardiovascular disease (16%). Age (odds ratio [OR] 1.05, confidence interval [CI], 1.01-1.09), SAPS 3 score (OR 1.04, CI, 1.01-1.08), the need for mechanical ventilation (OR 26.47, CI, 10.30-68.08), and vasopressor use (OR 3.34, CI, 1.37-8.13) were independently associated with hospital mortality. The performance of SAPS 3 and APACHE II scores was poor in this population and overestimated the mortality rates. CONCLUSION: Sepsis was the main reason for ICU admission in kidney transplant recipients, followed by cardiovascular disease. Age and disease severity were associated with hospital mortality.
Assuntos
Cuidados Críticos/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Tempo de Internação/estatística & dados numéricos , Complicações Pós-Operatórias/terapia , Transplantados/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Mortalidade Hospitalar , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Long-term efficacy and safety of de novo use of the mammalian target of rapamycin inhibitors (mTORi) have been evaluated primarily using registry data. METHODS: This was a pooled retrospective analysis of data obtained from 10 prospective randomized trials in de novo kidney transplant recipients (n = 581) receiving calcineurin inhibitors (CNIs) combined with sirolimus (n = 329), everolimus (n = 128), or antimetabolites (n = 124). RESULTS: There were no differences in patient (84.5 versus 80.9 versus 89.7%, P = 0.996), graft (65.4 versus 59.5 versus 73.1%, P = 0.868), and biopsy-confirmed acute rejection-free (78.1 versus 77.3 versus 79.0%, P = 0.976) survivals, respectively. The incidence of cytomegalovirus infection was lower (6 versus 3 versus 11%, P = 0.024) but treatment discontinuation was higher among patients receiving mTORi (66.0 versus 47.7 versus 31.5%, P < 0.001), respectively. At 5 years, median estimated glomerular filtration rate (49.6 versus 43.9 versus 53.2 mL/min, P = 0.006) was lower and the proportion of patients with proteinuria (53 versus 40 versus 23%, P < 0.001) was higher among patients receiving mTORi, respectively. CONCLUSIONS: The efficacy of de novo use of mTORi is comparable with that of antimetabolites in kidney transplant recipients receiving calcineurin inhibitor. Apart from the lower cytomegalovirus infection rate, the safety profile is unfavorable, showing higher treatment discontinuation rates and higher incidence of proteinuria.
Assuntos
Inibidores de Calcineurina/administração & dosagem , Imunossupressores/administração & dosagem , Transplante de Rim/métodos , Adolescente , Adulto , Idoso , Inibidores de Calcineurina/efeitos adversos , Everolimo/administração & dosagem , Everolimo/efeitos adversos , Feminino , Seguimentos , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Adulto JovemRESUMO
The chronic course of hepatitis E virus infection in immunosuppressed patients has been recently documented; however, clinical features and factors associated with this occurrence are not well known. The aim of this study was to evaluate the prevalence of previous or current HEV infection in renal transplant patients. One hundred ninety-two kidney transplant patients were studied and classified in three groups: G1-infected with hepatitis B and/or C virus; G2-patients with elevated ALT; G3-patients with normal ALT and no hepatotropic virus infection. Demographic, epidemiologic and clinical characteristics were compared between the groups. Patients with HEV infection (previous or current) were also compared to those who tested negative for HEV. HEV infection was detected using serologic (anti-HEV IgG) and molecular (HEV RNA) methods. Anti-HEV IgG was positive in 28 (15%) while HEV RNA was positive in 20 (10%). When both markers were considered, 44 (23%) patients showed evidence of previous or current HEV infection. However, both markers were concomitantly positive in only four cases (2%). In the comparative analysis, patients infected with HBV and/or HCV showed lower frequency of anti-HEV IgG (P = 0.009). There was no difference regarding demographic, epidemiologic and laboratory variable between viremic and non-viremic patients. In conclusion, past and current infection with HEV was a frequent finding among renal transplant recipients. Actively infected patients (HEV RNA positive) did not present distinct demographic and epidemiological characteristics or laboratory alterations suggestive of underlying liver damage. Therefore, infection with HEV can only be detected in immunosuppressed patients by systematic investigation of HEV RNA.
Assuntos
Vírus da Hepatite E/isolamento & purificação , Hepatite E/epidemiologia , Transplante de Rim , Transplantados , Adulto , Idoso , Feminino , Anticorpos Anti-Hepatite/sangue , Vírus da Hepatite E/imunologia , Humanos , Hospedeiro Imunocomprometido , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Prevalência , RNA Viral/sangueRESUMO
AIM: The angiotensin-converting enzyme 2 (ACE2) and its homolog, the angiotensin converting enzyme 1 (ACE), are involved in COVID-19 physiopathology. Alterations in the enzymatic structure, expression, and/or activity may influence the risk of infection and severity of disease. For this reason, we aimed to identify different allelic forms of ACE2 G8790A and ACE I/D polymorphisms in a Brazilian cohort and evaluate their impact on ACE and ACE2 activities and their association with COVID-19 susceptibility and severity. MAIN METHODS: A total of 549 COVID-19-negative and 270 COVID-19-positive participants from Ipaussu, Sao Paulo, Brazil, were recruited. ACE2 and ACE activities were measured by fluorogenic assays using MCA-Ala-Pro-Lys(Dnp) as the substrate for ACE2 and Z-Phe-His-Leu-OH (Z-FHL) and Hippuryl-His-Leu-OH (h-HL) as substrates for ACE. Genomic DNA was extracted from EDTA-peripheral blood, and the regions of the genes containing ACE2 G8790A and ACE I/D polymorphisms were amplified by PCR-restriction fragment length polymorphism and real-time PCR, respectively. KEY FINDINGS: The G allele of ACE2 G8790A polymorphism and D allele of ACE I/D polymorphism are associated with increased ACE and ACE2 activities. ACE activity ratio (Z-FHL/h-HL), an inflammatory marker, is increased in women with GG genotype and COVID-19-positive diagnosis. SIGNIFICANCE: For the first time, it was demonstrated that in females, the GG genotype is associated with increased ACE activity ratio (Z-FHL/h-HL) in the COVID-19-positive group. Elevated ACE activity ratio (Z-FHL/h-HL) is highly linked to inflammation and may justify the associations between the G genotype and COVID-19 severity of symptoms and outcomes.
RESUMO
Hepatitis E virus (HEV) causes acute and chronic hepatitis in organ transplant recipients. Serological evidence for HEV infection has been discovered in various population groups in Brazil, and a single acute case has been confirmed. To date, however, no cases of HEV infection in immunocompromised patients have been reported in Brazil. This study aimed to identify and characterize hepatitis E cases in renal transplant recipients in Brazil. A retrospective study was performed on 96 serum samples from renal transplant recipients with unexplained liver enzymes elevation. Three confirmed cases of HEV infection were identified that lacked seroconversion to HEV IgG antibodies. The prevalence of HEV in these patients was 3.1%. Using a sequence analysis of a 304-nucleotide fragment within ORF2, the strains were classified as genotype 3 with a low percent identity to previously characterized strains. This is the first report of hepatitis E infection in renal transplant recipients in Brazil, and the data indicate that a novel genotype 3 subvariant may be present and that further investigation is necessary to characterize the circulating HEV strains. In this setting, HEV infection should be considered as a potential cause of abnormal liver tests of unknown origin.
Assuntos
Vírus da Hepatite E/isolamento & purificação , Hepatite E/epidemiologia , Hospedeiro Imunocomprometido , Transplante , Adulto , Brasil/epidemiologia , Feminino , Genótipo , Hepatite E/virologia , Vírus da Hepatite E/genética , Humanos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Prevalência , RNA Viral/genética , Estudos Retrospectivos , Análise de Sequência de DNARESUMO
BACKGROUND: Kidney transplant recipients are at a high risk of opportunistic infection. The aims of this study were to describe the epidemiology, clinical features, and prognosis of abdominal tuberculosis (TB) in kidney transplant recipients. METHODS: All cases of abdominal TB that occurred in kidney transplant recipients at our center between 1998 and 2010 were retrospectively reviewed. Detailed demographic data, clinical profile information, and the treatment response were recorded. RESULTS: Among the 7833 kidney transplantations performed during the study period, eight patients (0.1%) developed abdominal TB. There were four men and four women in this group. The mean age of the patients was 44 ± 12 yr. The time from kidney transplantation to TB was 6.7 ± 3.4 yr. The symptoms were weight loss (87.5%), diarrhea (87.5%), fever (75%), abdominal pain (62.5%), and lower gastrointestinal bleeding (37.5%). The delay between the identification of the clinical symptoms and the diagnosis was an average of six months. The diagnosis was confirmed histopathologically for most patients. The cecum and ascending colon were the most common sites involved. Two patients required surgical intervention. Five patients received a 4-drug regimen, and three had hepatotoxicity. The median length of antituberculous therapy was nine (6-12) months. Five patients lost their graft. Overall, the hospital mortality was 12.5%. CONCLUSIONS: Kidney transplantation increases the risk of TB, particularly as an extrapulmonary disease. The symptoms of infection are often attenuated, leading to delayed diagnosis. Therefore, a careful approach to the patient and supportive data are necessary to make the final and timely diagnosis.
Assuntos
Dor Abdominal/diagnóstico , Obstrução Intestinal/diagnóstico , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias , Tuberculose Gastrointestinal/diagnóstico , Dor Abdominal/tratamento farmacológico , Dor Abdominal/etiologia , Adulto , Antituberculosos/uso terapêutico , Feminino , Seguimentos , Humanos , Obstrução Intestinal/tratamento farmacológico , Obstrução Intestinal/etiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/patogenicidade , Prognóstico , Fatores de Risco , Tuberculose Gastrointestinal/tratamento farmacológico , Tuberculose Gastrointestinal/etiologia , Adulto JovemRESUMO
Introduction: The combination of tacrolimus/mTORi compared to tacrolimus/mycophenolate (MMF) was shown to be safe in the TRANSFORM trial. For donors with a high KDPI (Kidney Donor Profile Index), however, there are no data to support the effectiveness of this regimen. The main objective of this study was to explore the influence of the KDPI on 12-month renal function (eGFR) in patients receiving mTORi or MMF. Methods: Multicenter cohort study of four Brazilian services that use the tacrolimus with mTORi as a protocol. Data from 2008 to 2018 of the tacrolimus/mycophenolate (MMF) and tacrolimus/mTORi (mTORi) regimens in renal transplant recipients over 18 years old were collected. For better homogeneity, the propensity score was used. Afterward, the method used for group selection ("match") was the K-nearest neighbor (KNN) method. New analyses were performed on this new balanced sample, and two different subsamples were constituted based on the median KDPI. Results: The global analysis (n = 870) showed that the major determinant of worse kidney function was high KDPI. Afterward, the three strata were analyzed. In the first stratum (KDPI up to 50), 242 patients were evaluated, with 121 in each group. The eGFR was 64â ml/min/1.73â m2 in the mTORi group compared to 63 in the MMF group, p = 0.4, and when imputed eGFR was evaluated, 61 in the mTORi and 53 in the MMF, p = 0.065. In the second stratum (KDPI from 50 to 85), 282 patients were evaluated, with 141 in each group. eGFR was 46â ml/min/1.73â m2 in mTORi compared to 48 in MMF, p = 0.4, and when imputed eGFR was evaluated, 40 mTORi and 41 MMF, p = 0.8. In the last stratum (KDPI higher than 85) with n = 126 and 63 cases per group, eGFR was 36â ml/min/1.73â m2 in mTORi compared to 39 in MMF, p = 0.2, and when imputed eGFR was evaluated, 30 mTORi and 34 MMF, p = 0.2. Discussion: The regimen using mTOR inhibitor is an effective and safe regimen when compared to the standard regimen. In addition, the scheme seems to offer additional protection against infections and may be an important ally in cases of high risk for these pathologies.
RESUMO
The diagnosis of hepatitis C virus (HCV) infection in hemodialysis patients is difficult particularly due to the presence of intermittent viremia. The aims of this study were: (a) to determine the prevalence of intermittent viremia in hemodialysis patients with anti-HCV antibodies who tested negative for HCV RNA by PCR at the first evaluation and (b) to evaluate the contribution of the transcription-mediated amplification method (TMA) to the diagnosis of viremia in the PCR-negative samples. One hundred and six patients with anti-HCV antibodies and an initial negative result for HCV RNA by PCR were included. An additional sample was collected for a second HCV RNA test by PCR after a minimum interval of 3 months and a positive result characterized intermittent viremia. HCV RNA was investigated by TMA in the PCR-negative sample of patients with intermittent viremia, and in the most recent sample from patients with PCR-negative results in both determinations. Intermittent viremia was observed in 60/106 (57%) patients (57% men; age: 45 ± 10 years). Fifty-one of the 60 negative samples from patients with intermittent viremia and 29/46 double-negative patients were tested by TMA. This assay detected viremia in 20/51 (39%) samples of intermittent viremia and in 2/29 (7%) of double-negative samples. The results showed that intermittent viremia is frequent in hemodialysis patients who tested negative for HCV RNA by PCR. Therefore, a second HCV RNA test is necessary for all HCV RNA-negative patients. The TMA assay appears to be the best first screening test for viremia in this population.
Assuntos
Hepacivirus/isolamento & purificação , Hepatite C/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , RNA Viral/isolamento & purificação , Viremia/diagnóstico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/genética , Diálise Renal , Virologia/métodosRESUMO
BACKGROUND: The influence of the conversion from cyclosporine (CsA) to everolimus (EVR) on the chronopharmacokinetics of mycophenolic acid (MPA) and its glucuronide (MPAG) and acyl glucuronide (acyl-MPAG) metabolites in patients receiving enteric-coated mycophenolate sodium (EC-MPS) has not been studied. METHODS: We evaluated daytime and nighttime steady-state MPA, MPAG, and acyl-MPAG pharmacokinetics in 24 stable kidney transplant recipients while receiving cyclosporine and 28 days after conversion from CsA to EVR. The effect of concomitant treatment and the circadian difference on AUC(t,ss) and C(max,ss) were assessed using a linear mixed model. RESULTS: After conversion from CsA to EVR, MPA AUC(t,ss) was 43% higher (29% daytime and 58% during nighttime), whereas MPAG AUC(t,ss) was 33% lower (35% daytime and 30% during nighttime) and acyl-MPAG AUC(t,ss) was 31% lower (36% during daytime and 26% nighttime). Compared with daytime, MPA AUC(t,ss) was 25% lower (32% with CsA and 17% with EVR), MPAG AUC(t,ss) was 24% lower (26% with CsA and 21% with EVR), and acyl-MPAG AUC(t,ss) was 26% lower (32% with CsA and 21% with EVR) during nighttime. After conversion from CsA to EVR, MPAG:MPA and acyl-MPAG:MPA AUC(t,ss) ratios were 50% lower but were not different during daytime compared with nighttime EC-MPS administration. There was no correlation between CsA or EVR concentrations with MPA, MPAG, and acyl-MPAG exposures during daytime and nighttime. At least 1 adverse event was reported in 70.8% of patients receiving EC-MPS and CsA and in 91.7% receiving EC-MPS and EVR. CONCLUSION: In stable kidney transplant recipients receiving EC-MPS and steroids, exposures to MPA, MPAG, and acyl-MPAG were lower during nighttime compared with daytime, both with CsA or EVR. This circadian effect on MPA exposure did not correlate with CsA or EVR concentrations or with altered MPAG and acyl-MPAG formation.
Assuntos
Ciclosporina/farmacocinética , Imunossupressores/farmacocinética , Transplante de Rim , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/sangue , Pró-Fármacos/farmacocinética , Sirolimo/análogos & derivados , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Adulto , Biotransformação/efeitos dos fármacos , Ritmo Circadiano , Estudos Cross-Over , Ciclosporina/efeitos adversos , Ciclosporina/sangue , Ciclosporina/uso terapêutico , Interações Medicamentosas , Monitoramento de Medicamentos , Quimioterapia Combinada/efeitos adversos , Everolimo , Feminino , Glucuronídeos/sangue , Humanos , Imunossupressores/sangue , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/farmacocinética , Ácido Micofenólico/uso terapêutico , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Pró-Fármacos/efeitos adversos , Pró-Fármacos/análise , Pró-Fármacos/uso terapêutico , Sirolimo/efeitos adversos , Sirolimo/sangue , Sirolimo/farmacocinética , Sirolimo/uso terapêutico , Comprimidos com Revestimento EntéricoRESUMO
Rapid tests (RT) have been widely used for screening of hepatitis C virus (HCV) in general population, but its performance in hemodialysis (HD) patients and mainly in kidney-transplant recipients (RTx) is less known. The aim of this study was to evaluate the accuracy of RT for detection of anti-HCV in HD and RTx patients. Patients were prospectively included subdivided in four groups according to the positivity for anti-HCV detected by conventional serology: (1) HD patients anti-HCV +, (2) HD patients anti-HCV -, (3) RTx patients anti-HCV +, and (4) RTx patients anti-HCV -. All patients were retested for HCV using the commercial kit Alere HCV® Bioeasy Rapid Test (Bioeasy Diagnóstica LTDA-Minas Gerais, Brazil) in capillary whole blood samples. During the period of study were included 46 HD patients anti-HCV+, 62 HD patients anti-HCV -, 53 RTx patients anti-HCV + and 56 RTx patients anti-HCV -. In patients on HD, the RT showed sensitivity (S), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and accuracy of 100%. In RTx patients, S of 96%, SP of 100%, PPV of 100% and NPV of 97% were found (accuracy of 98%). In conclusion, in patients on HD there was 100% agreement between RT and the conventional immunoassay. In the RTx group, although the agreement was not 100%, the RT performed very well when compared to conventional serology. This study demonstrates that the RT can be an alternative to conventional serology in HCV screening of patients on HD and RTx.